About Next-Gen Models
Many of the cancer cell lines that are commonly used in cancer research were established decades ago. These cell lines have been useful for in vitro experiments to study cancer biology, biochemistry, and drug targets. However, drawing conclusions about how in vitro observations may relate to clinical biology is challenging because cancer cell lines
- lack the cellular complexity and architecture of human tumors, which introduces possibility that genetic drift may have occurred after the cell line was established
- are not associated with clinical information from the patient
- genomic relatedness to the parent tumor is unknown, and molecular characterization including assessment of genomes and transcriptomes of these cell lines, until recently, were mostly unavailable
- from diverse racial and ethnic groups and rare cancers are seldom represented in currently available cell lines
The Human Cancer Models Initiative (HCMI) addresses the deficiencies in current models by collecting patients’ clinical data and assessing, as much as possible, the genomes and transcriptomes of the parent tumor, case-matched normal tissue, and the derived next-generation cancer model. All of the HCMI next-generation cancer models are derived from primary patient tissues. The information collected are made available to the end user through NCI’s Genomic Data Commons.
Next-Generation Cancer Models
Next-generation cell culture models, such as organoids, conditionally reprogrammed cells (CRC), or optimal growth condition models introduce the opportunity to propagate primary normal and cancer cells. The term organoid here refers to a three-dimensional (3-D) structure grown from tumor cells in vitro that comprises organ-specific cell types. The CRC methodology uses unique cell growth media supplemented with growth factors to enable cancer model development and growth for in vitro experiments. The organoid, CRC, and optimum growth condition methods have been used, with some modifications, to grow tumor tissues in research. The next-generation cancer models that result from the efforts of HCMI provide excellent tools to support precision oncology research and give insight into the pathways that influence tumor progression.
The goal of HCMI is to generate models from many human cancer subtypes, including breast, colorectal, glioblastoma, gastroesophageal, lung, melanoma, and pancreas. Models from rare adult and pediatric cancers have been developed by HCMI, including neuroblastoma, osteosarcoma, Wilms tumor, rhabdomyosarcoma, and Ewing sarcoma. Model generation from new cancer types is ongoing, including head and neck, kidney, ovarian, and endometrial cancers. The model list along with their associated case report forms (CRFs) will be updated as more cancers are represented by HCMI models in the future.
Developing Models to Address Cancer Disparities
NCI has made a strong commitment to decrease cancer health disparities by supporting model development from racially and ethnically diverse populations. The Center for Cancer Genomics (CCG) has partnered with the Center to Reduce Cancer Health Disparities (CRCHD) to support research supplement awards for collection of tumors and clinical data from racial and ethnic minority populations for next-generation cancer model development.
CCG Director Dr. Staudt has also discussed the importance of HCMI’s collaboration with the CRCHD in his blog post, Continuing Our Work in the Time of Two Pandemics.